PMID- 34044860 OWN - NLM STAT- MEDLINE DCOM- 20210624 LR - 20210624 IS - 1758-9193 (Electronic) VI - 13 IP - 1 DP - 2021 May 27 TI - Association of accelerated long-term forgetting and senescence-related blood-borne factors in asymptomatic individuals from families with autosomal dominant Alzheimer's disease. PG - 107 LID - 10.1186/s13195-021-00845-0 [doi] LID - 107 AB - BACKGROUND: Accelerated long-term forgetting has been identified in preclinical Alzheimer's disease (AD) and is attributed to a selective impairment of memory consolidation in which the hippocampus plays a key role. As blood may contain multiple senescence-related factors that involved in neurogenesis and synaptic plasticity in the hippocampus, we tested whether there is an association between blood-borne factors and accelerated long-term forgetting in asymptomatic individuals from families with autosomal dominant AD (ADAD). METHODS: We analyzed data of 39 asymptomatic participants (n = 18 ADAD mutation carriers, n = 21 non-carriers) from the Chinese Familial Alzheimer's Disease Network (CFAN) study. Long-term forgetting rates were calculated based on recall or recognition of two materials (word list and complex figure) at three delays comprising immediate, 30 min, and 7 days. Peripheral blood concentrations of candidate pro-aging factors (CC chemokine ligand 11 [CCL11] and monocyte chemotactic protein 1 [MCP1]) and rejuvenation factors (growth differentiation factor 11 [GDF11], thrombospondin-4 [THBS4], and secreted protein acidic and rich in cysteine like 1 [SPARCL1]) were evaluated in all participants. RESULTS: Despite normal performance on standard 30-min delayed testing, mutation carriers exhibited accelerated forgetting of verbal and visual material over 7 days in comparison with matched non-carriers. In the whole sample, lower plasma THBS4 was associated with accelerated long-term forgetting in list recall (beta = -0.46, p = 0.002), figure recall (beta = -0.44, p = 0.004), and list recognition (beta = -0.37, p = 0.010). Additionally, higher plasma GDF11 and CCL11 were both associated with accelerated long-term forgetting (GDF11 versus figure recall: beta = 0.39, p = 0.007; CCL11 versus list recognition: beta = 0.44, p = 0.002). CONCLUSIONS: Accelerated long-term forgetting is a cognitive feature of presymptomatic AD. Senescence-related blood-borne factors, especially THBS4, GDF11, and CCL11, may be promising biomarkers for the prediction of accelerated long-term forgetting. FAU - Yang, Jianwei AU - Yang J AD - Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 45 Changchun St, Beijing, China. FAU - Kong, Chaojun AU - Kong C AD - Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 45 Changchun St, Beijing, China. FAU - Jia, Longfei AU - Jia L AD - Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 45 Changchun St, Beijing, China. longfei@mail.ccmu.edu.cn. AD - Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China. longfei@mail.ccmu.edu.cn. AD - Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China. longfei@mail.ccmu.edu.cn. AD - Center of Alzheimer's Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China. longfei@mail.ccmu.edu.cn. FAU - Li, Tingting AU - Li T AD - Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 45 Changchun St, Beijing, China. AD - Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China. AD - Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China. AD - Center of Alzheimer's Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China. FAU - Quan, Meina AU - Quan M AD - Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 45 Changchun St, Beijing, China. AD - Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China. AD - Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China. AD - Center of Alzheimer's Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China. FAU - Li, Yan AU - Li Y AD - Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 45 Changchun St, Beijing, China. FAU - Lyu, Diyang AU - Lyu D AD - Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 45 Changchun St, Beijing, China. FAU - Li, Fangyu AU - Li F AD - Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 45 Changchun St, Beijing, China. AD - Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China. AD - Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China. AD - Center of Alzheimer's Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China. FAU - Jin, Hongmei AU - Jin H AD - Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 45 Changchun St, Beijing, China. AD - Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China. AD - Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China. AD - Center of Alzheimer's Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China. FAU - Li, Ying AU - Li Y AD - Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 45 Changchun St, Beijing, China. AD - Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China. AD - Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China. AD - Center of Alzheimer's Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China. FAU - Wang, Qigeng AU - Wang Q AD - Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 45 Changchun St, Beijing, China. AD - Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China. AD - Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China. AD - Center of Alzheimer's Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China. FAU - Jia, Jianping AU - Jia J AUID- ORCID: 0000-0003-4624-0336 AD - Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 45 Changchun St, Beijing, China. jiajp@vip.126.com. AD - Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China. jiajp@vip.126.com. AD - Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China. jiajp@vip.126.com. AD - Center of Alzheimer's Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China. jiajp@vip.126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210527 PL - England TA - Alzheimers Res Ther JT - Alzheimer's research & therapy JID - 101511643 RN - 0 (Bone Morphogenetic Proteins) RN - 0 (Calcium-Binding Proteins) RN - 0 (Extracellular Matrix Proteins) RN - 0 (GDF11 protein, human) RN - 0 (Growth Differentiation Factors) RN - 0 (Osteonectin) RN - 0 (SPARCL1 protein, human) SB - IM MH - *Alzheimer Disease/genetics MH - Bone Morphogenetic Proteins MH - Calcium-Binding Proteins MH - Extracellular Matrix Proteins MH - Growth Differentiation Factors MH - Humans MH - Memory Disorders/genetics MH - Mental Recall MH - Neuropsychological Tests MH - Osteonectin MH - Recognition, Psychology PMC - PMC8157428 OTO - NOTNLM OT - Accelerated long-term forgetting OT - Alzheimer's disease OT - Biomarkers OT - Blood-borne factors OT - Senescence COIS- The authors declare that they have no competing interests. EDAT- 2021/05/29 06:00 MHDA- 2021/06/25 06:00 PMCR- 2021/05/27 CRDT- 2021/05/28 06:14 PHST- 2021/02/27 00:00 [received] PHST- 2021/05/10 00:00 [accepted] PHST- 2021/05/28 06:14 [entrez] PHST- 2021/05/29 06:00 [pubmed] PHST- 2021/06/25 06:00 [medline] PHST- 2021/05/27 00:00 [pmc-release] AID - 10.1186/s13195-021-00845-0 [pii] AID - 845 [pii] AID - 10.1186/s13195-021-00845-0 [doi] PST - epublish SO - Alzheimers Res Ther. 2021 May 27;13(1):107. doi: 10.1186/s13195-021-00845-0.